1-((Phenylmethoxy)carbonyl)-3-piperidinebutanoic acid → Phenylmethyl 3-(4-hydroxybutyl)-1-piperidinecarboxylate

HRID 2038170Notes

Reaction equation

HRID 2038170 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:16][CH2:15][CH2:14][CH:13]([CH2:17][CH2:18][CH2:19][C:20](O)=[O:21])[CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C1COCC1>[OH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH:13]1[CH2:14][CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:10])[CH2:12]1

Participants

3

Reactant 1

HCID 448908311-((Phenylmethoxy)carbonyl)-3-piperidinebutanoic acid

Product 1

HCID 58306139Phenylmethyl 3-(4-hydroxybutyl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(1-{[(phenylmethyl)oxy]carbonyl}-3-piperidinyl)butanoic acid (commercially available, for example, from Astatech) (5.01 g, 16.41 mmol) in dry THF (40 mL) at 0° C. under nitrogen was added a solution of Borane-THF complex, (1M solution in THF) (49.2 mL, 49.2 mmol), dropwise over 1 hour. The mixture was allowed to stir at 0° C. and gradually allowed to warm to room temperature over 20 hours. The mixture was cooled in an ice bath and cautiously quenched with dropwise addition of MeOH (20 mL), stirred in the cold bath for 2 hours, then quenched further with 10% 2N HCl/MeOH (20 mL), stirred for 1 hour at room temperature and evaporated under reduced pressure. The residue was co-evaporated with methanol several times. The sample was purified by chromatography on silica (100 g, loaded in dichloromethane/EtOAc) using a gradient of 0-100% ethyl acetate-cyclohexane over 30 minutes collecting all 45 mL fractions on the Flashmaster II. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a colourless oil (4.55 g).

Workup

  1. customat 0° C.
  2. temperatureto warm to room temperature over 20 hours
  3. temperatureThe mixture was cooled in an ice bath
  4. customcautiously quenched with dropwise addition of MeOH (20 mL)
  5. stirringstirred in the cold bath for 2 hours
  6. customquenched further with 10% 2N HCl/MeOH (20 mL)
  7. stirringstirred for 1 hour at room temperature
  8. customevaporated under reduced pressure
  9. customThe sample was purified by chromatography on silica (100 g, loaded in dichloromethane/EtOAc)
  10. customover 30 minutes
  11. customcollecting all 45 mL fractions on the Flashmaster II
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-daa63c63593c4c8abc3278c437485cd9
Source dataset
uspto-grants-2013_11
Patent number
US08575340B2

Reaction notes

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